Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Kenneth W. Mahaffey, Meg J. Jardine, Severine Bompoint, Christopher P. Cannon, Bruce Neal, Hiddo J.L. Heerspink, David M. Charytan, Robert Edwards, Rajiv Agarwal, George Bakris, Scott Bull, George Capuano, Dick de Zeeuw, Tom Greene, Adeera Levin, Carol Pollock, Tao Sun, David C. Wheeler, Yshai Yavin, Hong ZhangBernard Zinman, Norman Rosenthal, Barry M. Brenner, Vlado Perkovic

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

BACKGROUND: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). METHODS: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. RESULTS: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). CONCLUSIONS: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.

Original languageEnglish (US)
Pages (from-to)739-750
Number of pages12
JournalCirculation
Volume140
Issue number9
DOIs
StatePublished - Aug 27 2019

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Secondary Prevention
Chronic Renal Insufficiency
Type 2 Diabetes Mellitus
Kidney
Primary Prevention
Renal Insufficiency
Cardiovascular Diseases
Standard of Care
Diabetes Mellitus
Hospitalization
Heart Failure
Stroke
Myocardial Infarction
Placebos
Canagliflozin
Clinical Trials

Keywords

  • canagliflozin
  • clinical trial
  • diabetes mellitus
  • primary prevention
  • renal insufficiency, chronic
  • secondary prevention

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups. / Mahaffey, Kenneth W.; Jardine, Meg J.; Bompoint, Severine; Cannon, Christopher P.; Neal, Bruce; Heerspink, Hiddo J.L.; Charytan, David M.; Edwards, Robert; Agarwal, Rajiv; Bakris, George; Bull, Scott; Capuano, George; de Zeeuw, Dick; Greene, Tom; Levin, Adeera; Pollock, Carol; Sun, Tao; Wheeler, David C.; Yavin, Yshai; Zhang, Hong; Zinman, Bernard; Rosenthal, Norman; Brenner, Barry M.; Perkovic, Vlado.

In: Circulation, Vol. 140, No. 9, 27.08.2019, p. 739-750.

Research output: Contribution to journalArticle

Mahaffey, KW, Jardine, MJ, Bompoint, S, Cannon, CP, Neal, B, Heerspink, HJL, Charytan, DM, Edwards, R, Agarwal, R, Bakris, G, Bull, S, Capuano, G, de Zeeuw, D, Greene, T, Levin, A, Pollock, C, Sun, T, Wheeler, DC, Yavin, Y, Zhang, H, Zinman, B, Rosenthal, N, Brenner, BM & Perkovic, V 2019, 'Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups', Circulation, vol. 140, no. 9, pp. 739-750. https://doi.org/10.1161/CIRCULATIONAHA.119.042007
Mahaffey, Kenneth W. ; Jardine, Meg J. ; Bompoint, Severine ; Cannon, Christopher P. ; Neal, Bruce ; Heerspink, Hiddo J.L. ; Charytan, David M. ; Edwards, Robert ; Agarwal, Rajiv ; Bakris, George ; Bull, Scott ; Capuano, George ; de Zeeuw, Dick ; Greene, Tom ; Levin, Adeera ; Pollock, Carol ; Sun, Tao ; Wheeler, David C. ; Yavin, Yshai ; Zhang, Hong ; Zinman, Bernard ; Rosenthal, Norman ; Brenner, Barry M. ; Perkovic, Vlado. / Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups. In: Circulation. 2019 ; Vol. 140, No. 9. pp. 739-750.
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TY - JOUR

T1 - Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

AU - Mahaffey, Kenneth W.

AU - Jardine, Meg J.

AU - Bompoint, Severine

AU - Cannon, Christopher P.

AU - Neal, Bruce

AU - Heerspink, Hiddo J.L.

AU - Charytan, David M.

AU - Edwards, Robert

AU - Agarwal, Rajiv

AU - Bakris, George

AU - Bull, Scott

AU - Capuano, George

AU - de Zeeuw, Dick

AU - Greene, Tom

AU - Levin, Adeera

AU - Pollock, Carol

AU - Sun, Tao

AU - Wheeler, David C.

AU - Yavin, Yshai

AU - Zhang, Hong

AU - Zinman, Bernard

AU - Rosenthal, Norman

AU - Brenner, Barry M.

AU - Perkovic, Vlado

PY - 2019/8/27

Y1 - 2019/8/27

N2 - BACKGROUND: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). METHODS: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. RESULTS: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). CONCLUSIONS: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.

AB - BACKGROUND: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). METHODS: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. RESULTS: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). CONCLUSIONS: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.

KW - canagliflozin

KW - clinical trial

KW - diabetes mellitus

KW - primary prevention

KW - renal insufficiency, chronic

KW - secondary prevention

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